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From pilot study grant to groundbreaking research

Fall 2016

In May 2001, SIR Foundation awarded to Sanjay Misra, MD, FSIR, its Pilot Grant for his research proposal, “Mechanisms of stenoses in hemodialysis grafts.” The foundation grant was just the beginning of the journey. “Early in one’s career, it’s important to establish credibility before applying for further funding,” Dr. Misra said. The data yielded from the Pilot Grant allowed Dr. Misra and his team to develop hypotheses that they could test in animal models before moving into clinical trials. They also developed the framework for understanding the biology of dialysis access failure and thus developed therapies that could reduce vascular injury.

A few years later, Dr. Misra combined preliminary data from that research with work supported by another grant to successfully apply for National Institutes of Health (NIH) funding. Dr. Misra’s first R01 grant centered on understanding the role of hypoxic injury and vascular endothelial growth factor-A in causing venous stenosis formation. This work led to the observation that bevacuzimab, given prior to the creation of arteriovenous fistulas (AVFs), was protective for venous stenosis formation. The team also observed the important role of inflammatory cytokines in venous stenosis, which led them to coat the outflow vein of an AVF with adipose-derived mesenchymal stem cells to reduce venous stenosis formation.

With the renewal of Dr. Misra’s grant, his team will focus on understanding how stem cells can be combined with pharmacological treatments to extend vascular access patency. The overarching goal of the study is to develop therapies that will help more than 600,000 patients on dialysis.

According to Dr. Misra, “It’s important to start with a safety study to ascertain whether cells are safe and if there is efficacy using them.” Dr. Misra has just received IND/IRB approval for a Phase I clinical trial using adipose-derived mesenchymal stem cells in patients undergoing placement of AVF at the Mayo Clinic and will be enrolling patients this summer in Rochester. The goal of this trial will be to improve vascular access function and patency.

With more than 90 papers published, 4 million dollars in funding and a clinical trial underway, Dr. Misra has clearly made the most of the SIR Foundation Pilot Grant he received 15 years ago. Dr. Misra said, “I think that the impact [of this research] is multilayered. It helps define IR as an innovative, forward-thinking specialty that looks at vascular disease beyond just balloons and stents and starts to unravel the biology of stenosis formation. This knowledge changes the way other specialists perceive us. My hope is that we will be able to use stem cells, instead of drugs, to treat vascular injury. We want to find out which patients it will serve best. If it doesn’t work, we want to find out why it doesn’t work, which is important. If it does work, can stem cells be used to help us in angioplasty or stenting? Can they be used in surgical bypass in periphery or adjunctive therapy in other areas? Regenerative therapies are great because you’re using your own tissue to heal. There is skepticism because of the complexity of the diseases we’re treating, but I hope that soon we will have a better idea of what works and what doesn’t.”

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Support SIR Foundation . . . support the future of IR

Through programs like the Pilot Grant, SIR Foundation has passionately encouraged and supported innovation for more than 20 years. The foundation’s grant programs form a continuum of funding opportunities that range from research training, to seed grants, to academic development grants. For more details on how you can support the foundation’s efforts, contact Terrianne Zeifman, SIR Foundation development director, at tzeifman@sirweb.org.